Linda: Fatigue from "too many prescription pills"

At 74 years of age, Linda was brought in by her daughter in the hopes of improving her overall energy level. Her daughter had been working with me on her own hormone imbalance issues for a few years, and felt so many beneficial effects that she was hoping her mother could be considered for the same type of therapy. She also recalls that Linda's energy had been much better in the past when she maintained estrogen replacement therapy for many years. In fact, she had just taken her mom to the gynecologist within her insurance network to request hormone therapy, but was advised against it. She described her mom as: "She has no life. She is on this Coumadin to thin her blood, and she can't eat any of the healthy vegetables that could potentially interfere with the Coumadin, not to mention she has to have regular frequent blood work. I'm also worried about her bleeding risk. She has no energy, and her life has been reduced down to just sitting in front of the TV for many hours a day, from 11AM-6PM, and asleep by 7PM. I think her terrible fatigue is due to her medications, especially the blood pressure medication, but her doctor won't change them." Linda's sleep also suffered terribly from getting up 4-5 times per night to urinate. She complained of hair loss, constipation, memory loss, restless legs, and admitted to eating a poor diet full of greasy, fried foods, with very little vegetables due to the dietary restrictions imposed by chronic use of Coumadin. Linda had multiple medical problems, including high blood pressure, high cholesterol, acid reflux, chronic pain from severe osteoarthritis which resulted in both hips being replaced, hypothyroidism, and gastric lymphoma related to H. pylori infection. She also underwent a hysterectomy that spared the ovaries at age 26 due to uterine prolapse, and was placed on oral Premarin estrogen replacement therapy at age 50, which she continued until age 68, when it was discontinued due to a possible blood clot in her lungs. Her medications included Coumadin, Atenolol, Simvastatin, Omeprazole, Aspirin, Levothyroxine, Vicodin, Celebrex, and vitamin D.

Before even reviewing her medical records, I alerted Linda and her daughter that the use of multiple medications, ie, "poly-pharmacy", especially in the elderly, was a definite concern, and that many of her medications could certainly be contributing to long-term fatigue and other side effects.  The Atenolol prescribed to control her blood pressure belongs to a specific class of medications called "beta-blockers", and is well-known to potentially cause fatigue. The Simvastatin prescribed to lower her cholesterol can also lead to fatigue, among other possible side effects, such as sleep disturbance and memory impairment. I was also concerned that her thyroid status be optimally managed in light of the primary complaint of fatigue. I requested a copy of her previous records, as the circumstances that led to the chronic use of Coumadin to thin her blood were unclear at the initial appointment. However, even before reviewing her medical records, I advised Linda to start working on improving her diet, as I suspected that this would reduce her need to take a chronic acid blocker such as Omeprazole. Furthermore, these very potent acid blockers are only FDA-approved for treatment of esophagitis (inflammation in the esophagus) for 4-8 weeks, and at the most for 12 months in those with chronic esophagitis that is healing more slowly.  Without any upper endoscopy to document ongoing esophagitis, Linda had been taking this medication chronically for years, significantly increasing the potential for chronic side effects, including reduced nutrient absorption and potential negative effects of the gut microbiome. I also counseled her on the importance of restful sleep, given the significance of the circadian rhythm in governing most of our bodily biochemical and molecular processes. I recommended that they speak to Linda's PCP about switching her blood pressure medication to a different class of medication that target the Renin-Angiotensin-Aldosterone System (RAAS) more specifically, rather than her current beta-blocker which is notorious for causing chronic fatigue. Furthermore, the RAAS drugs are actually anti-inflammatory and are protective in terms of vascular biology. I also cautioned them that she would need to slowly wean off the beta-blocker over 6 weeks in order to prevent rebound elevation in blood pressures. I asked her to start a slow taper down on her opioid pain medications, which were likely contributing to deranged sleep physiology, constipation, memory loss, and fatigue. I also advised a cautious dose reduction of her Simvastatin, given this medication is associated with fatigue and memory loss, as well as sleep derangements.

Linda's daughter tracked down a disc of her electronic medical records, which consisted of over 1300 pages of documents, a significant portion of which was simply repeatedly cut/pasted medical history from one visit to the next without any new information After spending 3+ hours studying her records, I was able to gather that Linda had maintained treatment on oral estrogen replacement therapy from age 50-68, and that it was discontinued when she presented to the Emergency Room for acute respiratory distress, and subsequently was diagnosed with pulmonary embolism (blood clot to the lungs). She was taken off all Premarin estrogen/hormone products, including very low dose vaginal estrogen for local bladder/vaginal benefits, and placed on long-term Coumadin, which she has been taking ever since. The presumed cause of her pulmonary embolism was the oral estrogen, and no further hematological evaluation was done thereafter to assess for other potential causes of blood clots, before or during long-term treatment with Coumadin, such as genetic mutations that might affect her liver's production of clotting factors. The records also indicated that shortly after stopping the oral estrogen therapy, Linda made multiple visits to her gynecologist complaining of terrible hot flashes and depression, as well as bladder irritation and repeated infections requiring use of antibiotics. Her gynecologist placed her back on low dose topical estrogen cream for vaginal/bladder health, which helped her bladder issues significantly. She was also prescribed multiple different types of antidepressants in an effort to treat her severe hot flashes without much improvement, though many did lead to side effects. In addition, I found that she had evidence of hyperparathyroidism (parathyroid hormone is involved in calcium regulation) and inflammation with iron overload, as denoted by elevated "ferritin", despite being borderline anemic chronically, and that neither of these had been evaluated. She was also borderline diabetic with an elevated HgbA1c at 6.0% (lab test to evaluate 3-mos blood sugar average that is typically monitored in diabetics), and had not had any dietary counseling to address her sugar dysregulation and obvious associated risks.

I met with Linda and her daughter again after reviewing the records, and in the interim, she reported already feeling noticeable improvement from just working on her diet and sleep, and slowly tapering down on her Omeprazole, Simvastatin, and Atenolol. She noticed her hair was growing in much better, and that she was down to waking up only 1-2 times per night now, which was a monumental improvement for her, having previously disrupted her sleep every 1-2hrs for years due to need to urinate. I advised her to go back to a regular schedule of low dose vaginal estrogen to help preserve her genito-urinary tissue integrity, and to also keep her free of repeated bladder infections. I gave them a copy of the most recent guidelines on the management of venous thromboembolic disease (blood clots in the venous system) per the American Chest Physicians, that are tailored to multiple specific categories of risk factors, and explained the recommendations in detail. Linda's primary risk factor for developing the pulmonary embolism was the years of orally dosed Premarin, which results in first-pass liver metabolism through the gastrointestinal tract. This is contrary to non-oral, transdermal route of administering estrogen therapy, which has actually been correlated with reduced clotting and inflammatory potential. Furthermore, Premarin is known to increase liver production of inflammatory proteins. For her specific situation, the American Chest Physicians guidelines indicate only 3-6 months of anti-coagulation (blood thinning), and furthermore, if there are indeed, reasons for long-term anti-coagulation, the non-vitamin K interference medications are now recommended over the traditional Coumadin (which works by interfering with the liver's production of Vitamin-K dependent clotting factors and requires frequent blood monitoring) due to ease of monitoring for the patient and improved quality of life. To take a more cautious approach, I recommended that they request a referral to a hematologist for a full evaluation of clotting risk to see if there really is any indication of long-term anti-coagulation, and if not, her Coumadin could be discontinued. I also handed them a copy of a scientific article that included an algorithm on the typical work-up for blood clots and the testing involved. In my mind, the benefits of blood thinning needed to be carefully balanced against the long-term risks of bleeding and quality of life concerns, as an elderly patient can easily trip, fall, and bleed from brain trauma or a hip fracture, which can have devastating consequences. Although Linda's daughter asked about putting her mother on hormone therapy, I advised that systemic hormone therapy was contra-indicated in Linda due to her age and her history of pulmonary embolism.

In addition, I gave Linda an extended tapering schedule to wean off of her Omeprazole and Atenolol completely, and to monitor her blood cholesterol while slowly tapering down to a lower dose of her Simvastatin, and commended Linda on the good progress she had made with her sleep and dietary improvements. I suspected that the long-term use of Omeprazole also led to numerous nutrient deficiencies and adversely interfered with the microbiome's effects on vascular biology, which is involved in the production of beneficial nitrous oxide by the blood vessels. I advised a thorough endocrine evaluation of her hyperparathyroidism, and recommended against any further iron supplementation, as I suspected she had anemia of chronic disease, with iron overload due to inappropriate chronic iron supplementation. I reviewed her pre-diabetic condition, and pointed out research indicating that chronic long-term Simvastatin is correlated with increased risk of diabetes through multiple mechanisms, including a slow toxic effect on the mitochondria of the pancreatic cells involved in synthesizing insulin for sugar regulation. We reviewed the importance of ongoing prudent diet and lifestyle measures, which can significantly turn around her multiple medical problems, thereby reducing the need for further medications.

A few weeks later, I received a beautiful thank-you card and letter from Linda and her daughter. The letter read:  "My Mom and I want to thank you from the bottom of our hearts! We had our meeting with my Mom's primary doctor today and all went well. He agreed to test for the blood clots and took her off the Coumadin immediately. I know you did a lot of extra research for my mom and we really appreciate everything you did. We had a huge victory and are so relieved by the outcome! We learned so much from you and really had fun doing so." There was also a separate hand-written note from Linda that stated: "I am so happy I got to meet you. I want to thank you for all your help. I'm feeling so much better and have more energy.  My life is good."

Linda's case illustrates the dangers of poly-pharmacy in an elderly patient, and that many times, drugs are prescribed readily to suppress a symptom, frequently associated with other systemic side effects, without getting down to the root cause of the problems. It also highlights the need to thoroughly assess the indications of certain medications such as chronic blood thinners, and weigh the benefits with the potential catastrophic risks of acute hemorrhage, especially in an elderly patient who is already at increased risk for falls, trauma, and fractures.  It is too bad that Linda was maintained for so many years on oral Premarin, which likely directly contributed to the development of pulmonary embolism. I would venture to say that this might not have happened had she been switched to a transdermal route of estrogen therapy earlier.